Oct4 and Hnf4alpha-induced hepatic stem cells attenuated hepatic function in liver injury model

Generation of expandable induce hepatic stem cells (iHSCs) has a potential for cell-based therapy and drug screening in liver disease. Recently many groups reported reprogramming of somatic cells into hepatocyte-like cells by direct conversion. However, the induced hepatocytes have limitations in proliferation, function and viability for cell therapy and drug development. We generated iHSCs which have properties including self-renewal and bipotency into hepatocytes and cholangiocytes. iHSCs-derived hepatocytes showed typical morphology and functions which include glycogen storage, low-density lipoprotein (LDL) uptake, Indocyanine green (ICG) metabolism, and Albumin secretion, and iHSCs-derived cholangiocytes also have functional characteristics of cholangiocytes, including cyst and tubules formation, cyst polarity, and the secretion of small substances by transmembrane channel protein. In addition, iHSCs attenuated liver injury, such as alcohol induced steatosis and carbon tetrachloride (CCl4) induced fibrosis models. Taken together, generation of functional iHSCs would be used in therapeutic applications. 7 samples were analyzed: pHep, primary Hepatocytes, 1 replicate, MEF, Mouse Embryonic Fibroblast , 4 replicates, iHep, induced Hepatic Stem Cells , 2 replicates)